205例羊水细胞嵌合体的产前诊断结果分析

目的分析205例羊水细胞嵌合体的产前诊断结果和妊娠结局,为嵌合体的遗传咨询和临床解释提供参考。方法对2018年1月至2019年11月中国医科大学附属盛京医院临床遗传科羊水细胞嵌合体病例的核型复查结果和基因组拷贝数测序(copy number variations sequencing,CNV-seq)检测结果进行回顾分析,并回访部分孕妇的妊娠结局。结果在7225例羊水核型结果中共有205例嵌合体,发生率为2.8%。其中Ⅰ级嵌合为153例,占比74.6%,多数为常染色体数目异常嵌合;Ⅱ级嵌合为18例,占比8.8%;Ⅲ级嵌合为34例,占比16.6%;Ⅱ级和Ⅲ级嵌合中多数为性染色体数目异常嵌合。20例患者核型复查结果显示,14例Ⅰ级和3例Ⅱ级嵌合病例的核型复查结果均为正常;1例Ⅱ级常染色体嵌合病例复查结果为Ⅲ级嵌合;2例Ⅲ级性染色体数目嵌合病例复查后均为正常核型。76例孕妇CNV-seq检测结果显示,53例Ⅰ级嵌合的CNV-seq检测结果均未提示嵌合。通过对比发现CNV-seq结果与核型结果不完全一致,包括CNV-seq是否检测到嵌合、嵌合比例、嵌合类型等。结论Ⅰ级嵌合和Ⅲ级嵌合的真伪性基本可以确定,孕妇有关Ⅱ级嵌合的后续选择需综合评估。单独应用CNV-seq检测染色体嵌合体仍存在一定的风险,核型检测嵌合体的优势不可替代,两种以上的实验方法联合应用有助于快速准确判定染色体嵌合体。

Analysis of prenatal diagnosis outcomes of 205 cases with mosaicism in amniotic fluid cells

Objective In order to provide references for the genetic counselling and clinical explanations of chromosome mosaicism,our research analyzed the prenatal diagnosis and pregnancy outcomes in 205 cases with mosaicism in amniotic fluid cells.MethodsWe retrospectively studied the resampling karyotypes and copy number variations sequencing(CNV-seq)results of the mosaicism cases in the Department of clinical genetics,Shengjing Hospital of China Medical University from Jan 2018 to Nov 2019,and several pregnancy outcomes were followed up.Results205 mosaicism cases were found in a total of 7225 cases,with the rate of 2.8%.Among them,153(74.6%)cases and 18(8.8%)cases were classified as levelⅠand levelⅡmosaicism separately,and levelⅢmosaicism was considered in the remaining 34 cases(16.6%).Most of levelⅠmosaicism cases were mosaic autosomal aneuploids,and mosaic sex chromosome aneuploids were majorities in levelⅡand levelⅢmosaicism.20 patients underwent resampling,in which normal karyotypes were separately diagnosed in 14 cases with levelⅠand 2 cases with levelⅡmosaicism,and 2 cases with levelⅢmosaic sex chromosome aneuploids;levelⅢwas re-identified in one case with levelⅡmosaic autosomal aneuploids.CNV-seq was performed in 76 cases and mosaicism was not detected in 53 cases with levelⅠmosaicism.With the comparison between karyotypes and CNV-seq results,we found that CNV-seq couldn′t detect the mosaicism in all of cases,and the constitutions of mosaicism were not entirely consistent.ConclusionThe authenticity of levelⅠand levelⅢmosaicism could be almost ascertained,and the subsequent options on levelⅡmosaicism should be evaluated comprehensively.The mosaicism could be missed by the single application of CNV-seq and the usage of karyotype was irreplaceable.The combination of multiple methods were useful for judging the mosaicism rapidly and accurately.